JPH02279666A - Production of carbamate and its intermediate - Google Patents

Abstract

PURPOSE: To obtain N-benzoylcarbamate in high yield by reacting an alkali metal salt of benzamide corresponding to the objective compd. with carbonate in the presence of an inert solvent and neutralizing the obtd. novel intermediate.

CONSTITUTION: An alkali metal salt of a compd. represented by formula I (wherein R¹ and R² are each a halogen, a 1-4C alkyl, a 1-4C alkoxy or CF₃ and, further, R¹ is H and R³ is H, a halogen, CH₃ or CF₃) formed by pref. using hydride or hydroxide of Li, Na or K is reacted with a compd. represented by formula II [wherein R is a 1-8C alkyl capable of having at least one halogen substituent or phenyl capable of having at least one substituent (a halogen, CH₃) in the presence of an inert solvent pref. within a temp. range from 0°C to the distillation temp. of the reaction mixture, and the obtd. alkali metal salt of a compd. represented by formula III, especially, a novel substance represented by formula IV (M is Li, Na or K) is neutralized to advantageously obtain the objective compd. represented by formula III useful as an intermediate for an insecticide or an insecticidal/miticidal agent.

COPYRIGHT: (C)1990,JPO

Description

DETAILED DESCRIPTION OF THE INVENTION Field of the Invention The present invention relates to a process for producing carbamates, particularly N-benzoyl carbamates, and to intermediates in this production.

[Conventional technology]

British Patent No. 1,324,293 discloses the formula [where M
is a lithium, sodium or potassium atom,
and R1, R1, Rs and R have the meanings according to any one of claims 1 to 4]. An alkali metal salt of N-benzoyl carbamate.

In formula C, A is a hydrogen atom, a halogen atom, a methyl group or a methoxy group, and B represents a hydrogen atom, a halogen atom, a methyl group or a methoxy group, provided that both A and B do not represent a hydrogen atom, X and Y can both be oxygen atoms, R and R can both be hydrogen atoms, and R8 especially represents a substituted phenyl group], and the same as insecticides. Use is disclosed.

The compound of the above formula in which A and B are both fluorine atoms, X and Y are both oxygen atoms, R and Rt are both hydrogen atoms, and R1 is 4-chlorophenyl is an insecticide diflubenzuron. [N-(4-chlorophenyl)-N'-(2゜6-difluorobenzoyl)
The corresponding compound in which urea is 1 and R is 4-trifluoromethylphenyl is the insecticide penfluron [N-(
2,6-difluorobenzoyl)-N'-(4-)lifluoromethylphenyl)urea 1. U.S. Patent No. 4.
No. 457.943 discloses, inter alia, an insecticide known as N-(2,4-difluoro-3,5-dichlorophenyl)-N'-(2,6-difluorobenzoyl)urea, i.e. teflubenzuron. ing.

European Patent Publication No. 11EP-A-161019 specifically describes N-(2,6-difluorobenzoyl)-N'-
(2-Fluoro-4-R2-chloro-4-(trifluoromethyl)phenoxy1phenylurea, an insecticide/acaricide known as flufenoxuron).

One method proposed in British Patent No. 1,324,293 for preparing compounds of the above formula in which R and Rt are both hydrogen is to convert an 0-ethyl carbamate compound of the formula R, -N)i .

[Page 11,
lines 13-18], the reaction is stated to be carried out in the presence of a solvent [page 14, lines 25-29], examples of suitable solvents being xylene, toluene, chlorobenzene and other similar Solvents with a boiling point above about 100° C. reactions are carried out at a temperature approximately equal to the boiling point of the solvent used. Example 10 thereof demonstrates the preparation of N-(2,6-dichlorobenzoyl)-N'-(3,4-dichlorophenyl)urea in this way with a yield of 90% using xylene as the solvent. It is listed. There is no description of the production of 0-ethyl carbamate.

European patent applications EP-A-174274 and E
P-A-219460 and British patent application CB-A
JP-A-2163430 all disclose types of N-benzoyl carbamates and their use in preparing various N-benzoyl-N-phenylureas having insecticidal activity by reaction with suitable substituted anilines. For example, British Patent Publication No. IGB-A-2163430 describes the formula [wherein R1 is hydrogen, halogen, CF, or CI-
4 alkoxy, R is halogen, C1-4 alkyl, CFs or C1-4 alkoxy, R3 is hydrogen, halogen, CFI or methyl, and R
discloses N-benzoyl-carbamates of C1-alkyl groups which can be substituted by halogen (preferably chlorine).

These pN-benzoyl-carbamates are stated to be obtainable in a manner known per se by reacting a suitable benzoyl isocyanate with a suitable alcohol or by reacting a suitable benzamide with a suitable ester of chloroformic acid in the presence of a base. (Page 3,
Lines 26-28].

It has now surprisingly been found that N-benzoyl carbamates can be prepared in high yields by a route which avoids the use of benzoyl isocyanate on the one hand and chloromace acid ester on the other hand.

[Key points of the invention]

Therefore, according to the present invention, -m formula [wherein R1 represents a hydrogen atom, a halogen atom, a Cl-4 alkyl group, a C1-4 alkoxy group, or a trifluoromethyl group, and Rz represents a halogen atom, a Cl-4 alkyl group] group, C1-4 alkoxy group or tri- or fluoromethyl group, R3 represents a hydrogen atom, halogen atom, methyl group or trifluoromethyl group, and R is 1 as appropriate.
C substituted by one or more halogen atoms
+-a represents an alkyl group or a phenyl group optionally substituted with one or more substituents selected from a halogen atom and a methyl group]. , Rt and R3 have the abovementioned meanings] in the presence of an inert solvent with a carbonate of the formula % ([) [wherein R has the abovementioned meanings] and neutralizing the alkali metal salt of the compound of formula I obtained.

formula! In and (2), R1 is hydrogen, fluorine or chlorine atom, R1 is fluorine or chlorine atom, and R3 is preferably hydrogen atom, particularly preferably,
Both R1 and R1 are fluorine atoms.

formula! In and (2), R is preferably a CI-6 alkyl group, conveniently a C1-, an alkyl group such as methyl or ethyl, or a phenyl group.

Compounds of formula II are described in the above-mentioned British Patent No. 1,324.293, US Pat.
No. 4, EP-A-219460 or British Patent No. 1
It is a known compound as described in 11GB-A-2163430, or it can be produced by a method similar to the method used to produce these known compounds.

Compound 2m is also a known compound, or can be produced in the same manner as the method for producing these known substances. For example, dimethyl carbonate, diethyl carbonate, diphenyl carbonate and dipropyl carbonate are commercially available, for example from Aldrich Chemie N, V, Brussels, Belgium.

Alkali metal salts of benzamides of formula II can be conveniently prepared from benzamides using alkali metal bases, such as hydrides or hydroxides of alkali metals (preferably lithium, sodium or potassium). Depending on the nature of the inert solvent, which may be a mixture of solvents, the alkali metal salt can be formed in situ from the alkali metal itself, if any.

The optimum reaction temperature depends, inter alia, on the nature of the carbonate and on the nature of the inert solvent. The reaction may conveniently be carried out at a temperature ranging from 0° C. to the distillation temperature of the reaction mixture.

Suitable inert solvents are, for example, ketones such as acetone and methyl ethyl ketone, esters such as ethyl acetate, secondary alcohols such as 2-butanol, chlorinated hydrocarbons such as dichloroethane or methylene chloride, For example, ethers such as tetrahydrofuran, aliphatic hydrocarbons such as cyclohexane, and aromatic solvents such as benzene, toluene, xylene or chlorobenzene.

Preferably, the molar ratio of the compound 2) to the compound of formula II is from 1:1 to 2:1.

If the inert solvent is not a secondary alcohol, a small amount of a secondary or tertiary hydroxy compound such as isopropanol, tertiary butanol or polycylic acid may be added to initiate the reaction. turned out to be advantageous.

The order in which the reactants are mixed is generally not critical.

However, if the alkali metal base used to form the alkali metal salt of the benzamide of formula II is a hydroxide, then the base is added to the compound of formula II and water is added before addition of the compound of formula II. Remove. Preferably, the molar ratio of alkali metal base to compound of formula H is l:
The ratio is 1 to 1.5:1.

If desired, the alkali metal salts of the compounds of formula I can be isolated, or they can be neutralized without isolation.

Neutralization of the alkali metal salt of the compound of formula I obtained can be conveniently carried out by treating the salt with an aqueous acid solution, for example an aqueous solution of hydrochloric acid, sulfuric acid, formic acid or acetic acid. Neutralization can be conveniently carried out at a temperature ranging from room temperature to the distillation temperature of the reaction mixture.

Furthermore, the present invention also provides an alkali metal salt of N-benzoyl carbamate itself of the formula: do.

[Examples] The present invention will now be further described by way of examples for illustrative purposes.

2.6-cyfluorobenzamide (79.5 g.

0.5 mol) and dimethyl carbonate (67 g, 0°7
6 mol) and acetone (250d) at O″C -II
The mixture was stirred and sodium hydride (16.6 g, 0.69 mol) was added. The reaction was monitored by hydrogen recovery and measurement. 13j! After 2 hours with recovery of hydrogen, the reaction mixture was warmed to room temperature (20° C.) and after hydrogen evolution had ceased, formic acid (98%, 35 g) was added.

Furthermore, a total of 151 hydrogen atoms were generated. The resulting mixture was filtered to remove precipitated sodium formate and the resulting acetone solution was evaporated to yield N-2,6-cyfluoropenzoyl-〇-methylcarbamate as a white solid (
109g, 97%, high performance liquid chromatography (H
A product with a purity of 97.2% by PLC, the remainder being dibenzfluoramide) was obtained.

NMR, CDC15, δ (ppm): 3.75, s
, 3H; 6.95, m-2H; 7.40, m-I
Hi 8.7, s, IH.

The mixture was stirred together. Sodium hydride (16,6g, 0
．． 69 mol) and then isopropanol (30 mol).
g) was added to initiate hydrogen evolution.

The reaction was monitored as in Example 1 by hydrogen recovery and measurement. After hydrogen generation stopped at 0°C,
The reaction mixture was warmed to room temperature (20°C) and formic acid (
35g) was added. Hydrogen evolution ceased and the precipitated sodium formate was removed by filtration and the solvent was evaporated to give the crude product as a white solid (106 g). This crude product was added to 1701d of toluene and warmed until a clear solution was obtained. Upon cooling to room temperature, a white solid precipitated and was filtered to give pure N-2,6-cyfluorobenzoyl-0-methylcarbamate (92 g, 8
5.5%) was obtained: m, p, 123-123.5°C
.

2.6-cyfluorobenzamide (79.5 g.

0.5 mol) and dimethyl carbamate (67 g, 0°7
6 mol) and ethyl acetate (250d) at 0°C.
- cyfluoropenzamide (79 g, 0.5 mol) and dimethyl carbamate (65 g, 0.72 mol) and 1.2
-dichloroethane (250II &) at room temperature (20″C)
) and sodium hydride (16,8
g, 0.7 mol) and then isopropanol (
30 g) was added to initiate hydrogen evolution. The mixture was cooled to 0° C. and the reaction was monitored by hydrogen recovery and measurement as in Example 1. first 10f
During the recovery of fi hydrogen, intense foaming of the reaction mixture was observed. After the reaction had stopped with evolution of 12.3ffi of hydrogen, formic acid was added and the reaction mixture was heated to reflux temperature. Hydrogen generation stops and filtration (80°
After removing the precipitated sodium formate in step C), the solvent was evaporated off and the crude product was purified as a white solid (106 g, HPLC
purity of 94%) was obtained.

Recrystallized from toluene (170d) to obtain pure N-2
,6-cyfluorobenzoyl-〇-methylcarbamate (99.7 g, 93%) was obtained: m.

P, 123~123.5°C0 l standing masu soil N--Jill Robben Lou- 2,6-cyfluoropenzamide (79.2 g.

0.5 mol) and dimethyl carbonate (65 g, 0°7
2 mol) and 2-butyl (250 d) were stirred together at 0 °C and sodium hydride (16.8 g, 0
．． 7 mol) was added. After the reaction stopped with the evolution of hydrogen 121, the reaction mixture was warmed to room temperature (20 °C),
And formic acid (32.5 g) was added. The mixture in the form of a thick slurry was heated to 80°C and filtered (80°C).
0″c), the precipitated sodium formate was removed. The solvent was evaporated and the crude product was reduced to a white solid (111 g, HPLC
Purity: 91.7%). Toluene (170
Recrystallization from m) gave pure N-2,6-cyfluorobenzoyl-〇-methylcarbamate (87 g.

81%) was obtained: m, p, 123-123.5°C
.

Difluorobenzamide (79 g, 0.5 mol), dimethyl carbonate (73 g, 0.8 mol) and tetrahydrofuran (200 ml) were stirred together at room temperature (20°C) and hydrogenated. Sodium (16g, 0.67mol)
The mixture was then cooled to 0° C. and Improper Tool (30 g) was added to start the reaction. After 12ffi of hydrogen evolved within 12 minutes, 13.21 was reached within 1 hour. After the reaction has stopped, the reaction mixture is warmed to room temperature (20 °C) and formic acid (31,2
g) was added. The mixture was warmed to 50°C, cooled to room temperature (20°C) and filtered to remove precipitated sodium formate. The obtained filtrate was evaporated to N-2
,6-cyfluoropenzoyl-〇-methylcarbamate as a white solid (109 g, 97%, purity 9 by HPLC).
7%, the remainder being difluorobenzamide).

NMR,, CDC1! In s, σ (ppm): 3.75
,S,3H86,95,rn, 2H near, 40,m
11 H: 8.7, s, LHs Seedling 1 116-difluorobenzamide (79 g, 0.5 mol), dimethyl carbonate (56 g, 0.6 mol) and xylene (400 m) were heated to room temperature (20°C). The mixture was stirred at room temperature and sodium hydride (13 g, 0.54 mol) was added. The reaction was started by adding isopropanol (45 g) and the reaction mixture was cooled to O'C and stirred for 20 h at 0 C until hydrogen evolution stopped (1
22 hydrogen evolution), and the reaction mixture was heated to room temperature (20"C).
) and filtered. The resulting white solid was washed with xylene (50s! x 3) and then with cyclohexane (5Qal!
120 g, 99%) was obtained.

NMRSD, in acetone, δ (ppm): 3.44
,s-3H;6.80,m,2HH7,20,m,
IH.

This sodium salt was added to acetic acid or hydrochloric acid (in each case 400 yd of 10 w/w % aqueous acid solution at room temperature (20°C)) to form N-2,6-cyfluorohenzoyl-〇-methylcarbame 14. Obtained in quantitative yield:
m, p, 123-1215°C.

2.6-difluorobenzamide (48g, 0°3 mol) and diphenyl carbonate (96g, 0°45 mol)
and toluene (400 g) were stirred together at 10 °C and sodium hydride (8 g, 0.33 mol, 16 g as a 50 w/w % dispersion of sodium hydride in mineral oil) was added. The temperature of the compound rose spontaneously to 44°C and the mixture grew completely to a solid material. After the temperature of the reaction mixture begins to drop, the precipitated solids are filtered off and N-
2゜6-difluorophenzoyl-0-phenylcarbamate sodium salt [I added to mixed N [(gull)]
R spectrum (cm-'): 3450 broad small,
3400 broad small, 2740 sharp small, 2680 sharp small, 1690 broad large, 1630 sharp small,
1550 broad large, 1240 sharp small, 1170 broad large, 1115 broad medium, 1005 sharp small,
970 sharp small, 905 sharp medium, 810 sharp small, 765 sharp, 725 sharp medium, 695 sharp medium] were obtained.

By stirring this salt in lQw/w% aqueous acetic acid solution (400d) at room temperature, N-2,6-cyfluoropenzoyl-〇-phenylcarbamate (80g, 95%) was obtained.
Obtained: m, p, 149°C02,6-difluorobenzamide (48 g, 0.3 mol), diethyl carbonate (45 g, 0.4 mol) and cyclohexane (25
0d) and stirred together at room temperature, sodium hydride (
7.5 g, 0.31 mol) was added. The reaction was started by the addition of Wasino 1/-inic acid, 0.5 g).The reaction mixture was then stirred at room temperature (20 °C) for 72 hours, and the precipitated solid material was then filtered. and washed with cyclohexane to remove N-2,6-cyfluorobenzoyl-ethylcarbamate sodium salt [congested (+all
) IR spectrum (C1l-'): 335
0 small broad, 3300 small broad, 3150 small broad, 1650 N1500 multiple peaks, 1225 large broad, 1135 medium broad, 1045 small sharp, 10
00 sharp, 970 sharp, 935 broad, 800-700 multiple peaks] were obtained.

Treatment with aqueous acetic acid similar to that in Example 7 resulted in N-2
, 6-cyfluoropenzoyl-〇-ethylcarbamate (57 g, 83%) at 2 m, p, 105°C.

2.6-cyfluoropenzamide (48 g, 0.3 mol) and potassium hydroxide pellets (19.68 g).

A mixture of oleic acid (1.38 g) and toluene was subjected to azeotropic distillation for 1.5 hours.

dife, -carbonate (66 g, 0.31 mo/
After addition of L+) and a further 15 minutes at distillation temperature, the mixture was cooled to room temperature. The precipitated solid was filtered from the reaction mixture and treated with aqueous acetic acid as in Example 7 to give N-2,6-cyfluoropenzoyl-
Phenyl carbamate (64g.

77 yuan) was obtained: m, p, 149°C.

Using a similar procedure as in Example 9 but using lithium hydroxide in place of potassium hydroxide, N-2,6-cyfluoropenzoyl--ethylcarbamate lithium salt was -cyfluoropenzoyl-〇-ethyl carbamate (m, p, 105°C) was prepared.

[rR spectrum in mull (cm-'
): 3350 broad, 3180 broad, 1
650~15001500 more! 250 broad,
1155 Broad Small, 1120 Broad Small, 1050 Broad Small, 1000 Sharp Medium, 955 Shielder-88
0 sharp small, 810-690 multiplex small and medium peaks].

Medium, 191 Shear) Lt Dar, 750 Shi+-7' Medium, 71
5 sharp].

Claims (8)

[Claims] (1) General formula▲There are mathematical formulas, chemical formulas, tables, etc.▼(I) [In the formula, R^1 is a hydrogen atom, a halogen atom, C_1_-
_4 alkyl group, C_1_-_4 alkoxy group or trifluoromethyl group, R^2 is a halogen atom,
C_1_-_4 alkyl group, C_1_-_4 alkoxy group or trifluoromethyl group, R^3 represents a hydrogen atom, halogen atom, methyl group or trifluoromethyl group, and R appropriately represents one or more halogens. When producing N-benzoyl carbamate of the general formula [C_1_-_8 represents an alkyl group substituted by an atom or a phenyl group optionally substituted by one or more substituents selected from a halogen atom and a methyl group] ▲There are mathematical formulas, chemical formulas, tables, etc.▼(II) [In the formula, R^1, R^2 and R^3 have the above meanings] In the presence of an inert solvent, an alkali metal salt of benzamide of the formula N-benzoyl, characterized in that it is reacted with a carbonate of RO-CO-OR (III) [wherein R has the above meaning] and the resulting alkali metal salt of the compound of formula I is neutralized. Method for producing carbamates. (2) R^1 is hydrogen, fluorine or chlorine atom, and R
2. The method according to claim 1, wherein ^2 is a fluorine or chlorine atom, and R^3 is a hydrogen atom. (3) The method according to claim 1, wherein R^1 and R^2 are both fluorine atoms. (4) The method according to claim 1, 2 or 3, wherein R is a C_1_-_6 alkyl group or a phenyl group. 5. A process according to claim 1, wherein a hydride or hydroxide of lithium, sodium or potassium is used to form the salt of the benzamide of formula II. (6) The method according to any one of claims 1 to 5, wherein the reaction is carried out at a temperature ranging from 0°C to the distillation temperature of the reaction mixture. (7) General formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (IV) [In the formula, M is a lithium, sodium or potassium atom, and R^1, R^2, R^3 and R are claims An alkali metal salt of N-benzoyl carbamate having the meaning as defined in any one of 1 to 4 above. (8) N-benzoyl carbamate of formula I produced by the method according to any one of claims 1 to 6.